Skin cancer is the most common form of cancer seen in the world today. The three most common types of skin cancer include basal cell carcinoma (BCE), squamous cell carcinoma (SCC), and malignant melanoma (MM). One in five Americans will develop some form of skin cancer at some point in their lives, and it is estimated that over one million Americans will develop some form of skin cancer each year. Malignant melanoma is one of the deadliest types of cancer and has been increasing at an alarming rate. In just the last decade, its instance has doubled and it is predicted that one in 105 Americans will fall victim to this disease.
Sun exposure has been implicated in the etiology of BCE, SCC and MM. The epidemic rise in the rate of these cancers is thought to be directly related to substantial increases in our population's outdoor activities and the desire, over the past several decades, for a "tanned" skin appearance. Pre-malignant, actinic keratoses are common skin growths believed to be induced by solar exposure, and have the potential for developing into skin cancer in upwards of 20% of cases. They often appear on the skin years before the development of cutaneous carcinomas. Malignant melanoma often develops in areas of the body where there has been previous solar damage.
It is considered a standard of care to eradicate as many actinic keratoses as possible with the least amount of discomfort, inconvenience and trauma (morbidity), for the patient. Since it has been shown that the total number of actinic keratoses increases if left untreated, any therapy that produces a statistically significant decrease in their number would be considered effective treatment.
Surgical removal of actinic keratoses is not always possible or desirable. Surgery is not practical when many small keratoses are present, and the scarring produced by surgery is generally unacceptable for exposed, relatively visible areas of the skin. Furthermore, it is believed that, in the early stages of their development, many keratoses are very small so as to be invisible to the naked eye and hence difficult or impossible to remove surgically.
Topically applied, chemical agents such as 5-fluorouracil (5-FU) or masoprocol have been employed to eradicate actinic keratoses. While 5-FU has demonstrated efficacy for this purpose, it has been found to cause pain, itching, skin inflammation, ulceration and cosmetic disfigurement often so severe that patients must avoid being seen in public, because their appearance may cause fear or revulsion, thus making its therapeutic use unacceptable to many individuals. These effects also preclude the use of 5-FU over large areas of the skin to treat incipient and/or microscopic keratoses. Problems associated with the use of 5-FU have been recognized in the prior art, and U.S. Pat. No. 4,234,599 discusses the problems of 5-FU therapy and proposes the use of certain carboxylic acids, (particularly hydroxy acids and keto acids) as well as their esters and amine salts as substitutes for 5-FU in the treatment of actinic as well as non-actinic keratoses.
Various carboxylic acid compounds, particularly the halogenated carboxylic acids, the keto acids and the alpha hydroxy carboxylic acids, and especially glycolic acid and lactic acids, (as well as their esters, salts and lactones), are widely used at present as superficial skin peeling agents. It has been found that their use can produce cosmetic improvements in the appearance of the skin, but they have not been very effective in removing actinic keratoses.
It will thus be appreciated that there is a need for a topically active agent which is effective in removing actinic keratoses, while avoiding the undesirable side effects of prior art preparations. The present invention provides a composition which effectively removes actinic keratoses without severe side effects. The composition may be applied to relatively large areas of skin to treat macroscopic keratoses and to prevent the development of incipient keratoses. These and other advantages of the present invention will be readily apparent from the discussion, description and examples which follow.